The Ro/SS-A autoantigen is a complex ribonucleoprotein. Autoantibodies against the components of this complex are frequently found in patients with lupus erythematosus and S jogren s syndrome. Some molecules involved in this complex are known, including a 52 kDa protein (Ro 52), a 60 kDa protein (Ro 60) an dhYRNAs. Recently, both in vitro and in vivo studies in our lab have further suggested that a third protein, calreticulin (CR), which has long been suspected to be a component of the Ro/SS-A complex does, in fact, bind to hYRNA and the 52 kD Ro polypeptide. However, the molecular interactions between proteins and proteins-RNAs within the Ro/SS-A particle are still poorly understood. Using recombinant proteins to systematically study proteins-protein interactions within this particle could help us better understand the formation of this complex at a molecular level. Yeast two-hybrid analysis as well as in vitro protein-protein interaction studies will be performed to examine such interactions among these proteins. The domains of interacting proteins will be dissected in detail to identify the protein motifs responsible for the contacts. Searching other protein partners which will interact with constituents of this complex by the approach of screening a yeast two-hybrid library has revealed an interaction between Ro 52 and the Fc region of IgG. Detailed examination of such interaction will be further studied in an in vitro assay and in a mammalian system.